Transgenic mice carrying the SV40 early control region and large T antigen gene consistently develop tumors of the choroid plexus. The aims of the proposed experiments are: (1) to assess the ability of specific mutants of T antigen to mediate choroid plexus tumorigenesis; (2) to address the role of p53 in SV40-mediated tumorigenesis; and (3) to determine whether T antigen or mutant T antigen proteins demonstrate any tissue-specificity in their oncogenic activity. Four T antigen mutants will be tested for their ability to generate choroid plexus tumors in transgenic mice after microinjection of the mutant DNAs into single-cell embryos. These mutants are impaired in their ability to transform some cells in culture but not others and they differ with respect to their other phenotypes. The distribution and level of T antigen expression in the tissues of the transgenic mice will be determined, and the animals will be observed for the characteristic development of choroid plexus tumors. The mouse p53 cDNA linked to the SV40 early transcriptional control region will also be used to generate transgenic mice. If the resulting mice express significant levels of p53 in the choroid plexus, they will be bred with transgenic mice that express SV40 large T antigen. The effect, if any, of p53 expression by itself and in conjunction with T antigen will be determined. The wild type and mutant T antigen genes will be placed under the control of two different transcriptional regulatory elements (the RSV LTR and the wild type polyoma virus enhancer) in an attempt to express them in a multitude of differentiated cell types in the mouse. Transgenic mice will be generated using the hybrid gene constructs and the tissue distribution of expression and tumor formation will be assessed.